Friedreich Ataxia: From Genetics to Mechanism to Clinical Features

Friedreich ataxia is a slowly progressive neurodegenerative disorder caused by GAA expansions in the FXN gene that lead to decreased transcription of the mRNA coding for frataxin protein. Such deficiency leads to impaired iron sulfur cluster synthesis and various components of mitochondrial dysfunction. These events have been modeled in cellular and animal models, leading to assessment of many potential therapeutic agents based on enhancement of mitochondrial function or mitigation of frataxin deficiency. One agent, though not curative, has been approved for adults with Friedreich ataxia, but many approaches remain in therapeutic development.